Mechano-chemical principles guiding membrane remodeling and curvature induced by small transmembrane proteins

• Applicant: Professor Dr. Dirk Schneider
• Subject Area: Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 511987215

Membrane remodeling and high curvature are important steps in the formation and dynamics of several organelles, such as the thylakoid and the endoplasmic reticulum membrane network. Transmembrane proteins, such as reticulons as well as members of the CurT family of proteins, are crucially involved in membrane bending in pro- and eukaryotes. However, the mechano-chemical principles guiding membrane curvature generation by transmembrane proteins are not yet understood. In this proposal, we will focus on a cyanobacterial protein (SynCurT) that modulates the organization of the thylakoid membrane system as a model system to study and understand membrane curvature induced by transmembrane proteins. In general, the bending propensity of transmembrane proteins, such as SynCurT, could arise from varying factors, such as the wedge-like domain or the flanking amphipathic helices. It is therefore the major goal of the current project to delineate the mechanistic and structural basis of how SynCurT induces membrane curvature. Towards this goal, a detailed experimental analysis of protein-protein interactions, as well as of protein-lipid interactions will be performed, supplemented by a computational approach (performed by our collaboration partner). In the first step, we will analyze the propensity of the full-length proteins as well as of mutants and truncated constructs to curve membranes using in vitro assays. In the next step, the association of SynCurT will be studied by in vitro and in vivo assays (as well as via simulations). Specific and non-specific lipid effects in membrane remodeling and curvature generation will be studied by considering the unique composition of cyanobacterial membranes. These effects will be delineated by systematically varying the membrane lipid composition. Overall, the proposed project will be an important step to understand the role of small transmembrane proteins in membrane remodeling in general, as well as in the context of the thylakoid membrane architecture.

• DFG Programme: Research Grants